ARTICLE
Nocardiosis is an uncommon infection caused by the ubiquitous bacterium
Nocardia, and can be divided into systemic and cutaneous types.
Systemic nocardiosis is the more common form and begins almost exclusively
in the respiratory tract [1]. Cutaneous involvement may develop as one
of four types: 1. mycetoma, 2. lymphocutaneous infection, 3. superficial
skin infection such as abscesses and cellulitis or granulomas, 4. disseminated
disease with skin involvement [2].
The Nocardia species commonly pathogenic in man include N.
asteroides, N. brasiliensis, N. farcinica and N. caviae. Skin
infections due to N. brasiliensis most often occur in non-compromised
hosts, whereas N. asteroides is primarily a systemic, opportunistic
infection of compromised hosts. N. asteroides is the most frequent
cause of nocardiosis in Italy as well as in United States [1, 3, 4].
Case report
A 37-year-old Italian female was seen in our department because of the
presence of multiple, brown-violaceous nodules on the right leg.
Since the age of 24 years, she had suffered from systemic lupus erythematosus
with hepatic, renal, ocular, genital and mucosal involvement. For the
past ten years she had been treated uninterruptedly with systemic corticosteroids.
The patient had had multiple, asymptomatic, brown-violaceous, suppurative
nodules and plaques on the right leg for two months. Lesions were indurated,
partially ulcerated, varying in size from 1 to 3 centimeters (Fig.
1). No superficial lymph node swelling was noted. A biopsy specimen
of a nodule showed a dense inflammatory infiltrate in the middle and deep
dermis. It consisted of neutrophilic granulocytes, lymphocytes, histiocytes
and some scattered giant cells arranged around a cavity which,
on hematoxylin and eosin staining, appeared empty. Pas and Grocott stains
showed in the cavity, filamentous bacilli which were also visible on Ziehl-Nielsen
staining (Fig. 2A). Cultures
on blood agar grew small, white, irregular and rough colonies with a mouldy
smell typical of Nocardia (Fig.
2B), while no other bacteria, including mycobacteria, were cultivated
from the same specimens. Laboratory studies were significant for a WBC
count of 3.2/ml, hemoglobin concentration of 11.7 g/dl, and an altered
liver function test (GOT 102 U/L, GPT 73 U/L), most likely due to the
underlying lupus erythematosus. Instrumental examination revealed no pulmonary
or visceral localization.
The clinical picture and microbiological findings
supported the diagnosis of primary cutaneous nocardiosis. The patient
was treated for one month with cotrimoxazole twice daily, with poor response.
Indeed, the antibiotic sensitivity test reported a resistance to sulphonamides
and a sensitivity to imipenem which was immediately administered three
times a day and continued for two months. Within four weeks there was
a marked improvement, and complete resolution, with skin hyperpigmentation,
occurred within three months. No relapse was observed 6 months later.
Discussion
Nocardiosis is caused by a bacterium belonging to the Actinomycetes
order, found as saprophytes in the soil. The Nocardia are gram-positive,
irregularly staining, with fine, branching filaments. Infection may occur
after direct inoculation into the skin or by inhalation and may be localized
to the skin or it may involve the lungs, disseminating to virtually any
organ. Predisposing factors include immunosuppression in AIDS, solid tumors,
lung diseases, hematological malignancies or long-term steroid or other
immunosuppressive therapies. Long term corticosteroid therapy is the most
likely cause of infection in our patient. The site of the lesion, despite
no clear history of trauma, favours the hypothesis of a direct skin inoculation.
Clinical and histopathological features of the lesions suggest it falls
into the third group of cutaneous nocardiosis [2].
Primary cutaneous nocardiosis without dissemination
is a very rare condition [5], although there are few statistical studies
available in the literature. Mark et al. found a 4% incidence of
cutaneous localization in nocardial infections [6]. Farina and co-workers
reported an incidence of 4 out of 30 patients with soft tissue involvement
only, with no mention of any cutaneous localization [1]. On the other
hand, primary cutaneous infection is probably underestimated, because
it is rarely suspected, it may simulate other skin conditions, it may
coexist with other more easily identified diseases, and finally, because
diagnostic tools are not always readily available. In our patient, the
first diagnosis was mycobacteriosis, based on the finding of filamentous
structures typical of this disease on Ziehl Nielsen staining. Only the
cultures performed in IUTM (International Union of Tubercolosis Medium)
allowed the final diagnosis of cutaneous nocardiosis. In this medium,
growth of Nocardia was very fast, whereas the growth of mycobacteria
in IUTM would take much longer. Identification of Nocardia at the
species level through the test for decomposition of adenine, caseine,
hypoxanthine, tyrosine, urea and xanthine was not possible in our laboratory.
Because N. brasiliensis is virtually never isolated from European
patients [1] and N. asteroides is normally the cause of infections
in immunosuppressed hosts [1, 6], we could speculate that N. asteroides
was likely to be the etiologic agent in our patient. Sulphonamides are
the drug of choice for nocardiosis, but resistance has also been reported
[1, 7] as was the case for our patient. Minocyclin, the second drug of
choice [2, 8], was not administered because of its side effect of exacerbating
systemic lupus erythematosus. Imipenem resulted in complete resolution
within three months, in agreement with other observations on the efficacy
of this drug [1, 9, 10]. Because of several reported cases of primary
cutaneous nocardiosis that subsequently disseminated [2, 11], a strict
follow-up of the patient will be required.
REFERENCES
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Italy from 1982 to 1992. Scand J Infect Dis 1995; 27: 23-7.
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Dermatol 1985; 13: 125-33.
3. Beaman BL, Burnside J, Edwards B, et al. Nocardial infections
in the United States. J Infect Dis 1976; 134: 286-9.
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lymphoma. Int J Dermatol 1992; 31: 178-9.
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J Med Vet Mycol 1992; 30 (suppl. 1): 317-31.
10. Schiff TA, Goldman R, Sanchez M, et al. Primary lymphocutaneous
nocardiosis caused by an unusual species of Nocardia: Nocardia transvalensis.
J Am Acad Dermatol 1993; 28: 336-40.
11. Vogel PS, Heimer WL, Sau P, et al. Primary cutaneous nocardia
infection due to Nocardia asteroides. Int J Dermatol 1993; 32:
811-2.
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